Daprodustat + GemfibrozilContraindicated
Strong CYP2C8 inhibitor causing marked increase in daprodustat exposure. Contraindicated with DAPRODUSTAT.
Source: NLP:daprodustat
Daprodustat Interactions
Brand names: Jesduvroq
Hypoxia-inducible Factor Prolyl Hydroxylase Inhibitor · Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors
Route: Oral
FDA Black Box Warning
WARNING: INCREASED RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, and THROMBOSIS OF VASCULAR ACCESS JESDUVROQ increases the risk of thrombotic vascular events, including major adverse cardiovascular events (MACE) [see Warnings and Precautions ( 5.1 )] . Targeting a hemoglobin level greater than 11 g/dL is expected to further increase the risk of death and arterial venous thrombotic events, as occurs with erythropoietin stimulating agents (ESAs), which also increase erythropoietin levels [see Warnings and Precautions ( 5.1 )] . No trial has identified a hemoglobin target level, dose of JESDUVROQ, or dosing strategy that does not increase these risks [see Dosage and Administration ( 2.4 )]. Use the lowest dose of JESDUVROQ sufficient to reduce the need for red blood cell transfusions [see Dosage and Administration ( 2.4 )] . WARNING: INCREASED RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, and THROMBOSIS OF VASCULAR ACCESS See full prescribing information for complete boxed warning. • JESDUVROQ increases the risk of thrombotic vascular events, including major adverse cardiovascular events (MACE). ( 5.1 ) • Targeting a hemoglobin level greater than 11 g/dL is expected to further increase the risk of death and arterial venous thrombotic events, as occurs with erythropoietin stimulating agents (ESAs), which also increase erythropoietin levels. ( 5.1 ) • No trial has identified a hemoglobin target level, dose of JESDUVROQ, or dosing strategy that does not increase these risks. ( 2.4 ) • Use the lowest dose of JESDUVROQ sufficient to reduce the need for red blood cell transfusions. ( 2.4 )
Contraindications
4 CONTRAINDICATIONS JESDUVROQ is contraindicated in patients: • Receiving a strong CYP2C8 inhibitor such as gemfibrozil [see Drug Interactions ( 7.1 ), Clinical Pharmacology ( 12.3 )] . • With uncontrolled hypertension [see Warnings and Precautions ( 5.3 )] . • Strong cytochrome P450 2C8 (CYP2C8) inhibitors such as gemfibrozil. ( 4 ) • Uncontrolled hypertension. ( 4 )
Pregnancy & Breastfeeding
8.1 Pregnancy Risk Summary Available data with JESDUVROQ use in pregnant women are insufficient to establish a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks to the mother and the fetus associated with CKD ( see Clinical Considerations ) . Daprodustat administered orally to pregnant rats and rabbits during the period of organogenesis was associated with adverse fetal outcomes, including embryonic and fetal loss and reduced fetal weight, at doses that caused maternal toxicity and polycythemia ( see Data ). Advise pregnant women of the potential risk to the fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk: CKD in pregnancy increases the risk for maternal hypertension, preeclampsia, miscarriage, stillbirth, preterm delivery, low birth weight infants, and polyhydramnios. Data Animal Data : Daprodustat was orally administered to pregnant rats at 0.5, 7, or 60 mg/kg/day from gestation day 6 to gestation day 17 during the period of organogenesis. No adverse effects were observed at doses less than or equal to 7 mg/kg/day (3 times the maximum recommended human dose [MRHD] based on body surface area). Daprodustat administration resulted in post-implantation loss, increased embryofetal death, and reduction in skeletal ossification in rats at a dose of 60 mg/kg/day (24 times the MRHD based on body surface area), which was associated with maternal toxicity (reduced body weight gain or weight loss). Maternal toxicity occurred at doses associated with polycythemia. Daprodustat was orally administered to pregnant rabbit
3 interactions on record
Moderate CYP2C8 inhibitor increasing daprodustat exposure. Requires dose reduction by half and hemoglobin monitoring.
Source: NLP:daprodustat
Daprodustat + RifampinModerate
CYP2C8 inducer may decrease daprodustat exposure and result in loss of efficacy. Monitor hemoglobin and adjust dose accordingly.
Source: NLP:daprodustat